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Oncotarget Jan 2017The chemopreventive effect of 5-aminosalicylic acid (5-ASA) in patients with inflammatory bowel disease (IBD) has been widely studied; however, the results remain... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND AIMS
The chemopreventive effect of 5-aminosalicylic acid (5-ASA) in patients with inflammatory bowel disease (IBD) has been widely studied; however, the results remain conflicting. The aim of this study was to systematically review the literature and update evidence concerning effects of 5-ASA on the risk of colorectal cancer (CRC) and dysplasia (Dys) in patients with ulcerative colitis (UC) or Crohn's disease (CD).
RESULTS
5-ASA showed a chemopreventive effect against CRC/Dys in IBD patients (OR = 0.58, 95% CI: 0.45-0.75). However, this effect was significant only in clinical-based studies (OR = 0.51; 95% CI: 0.39-0.65), but not in population-based studies (OR = 0.71; 95% CI: 0.46-1.09). Moreover, this effect was noticeable in patients with UC (OR = 0.46, 95% CI: 0.34-0.61), but not in CD (OR = 0.66, 95% CI: 0.42-1.03), and on the outcome of CRC (OR = 0.54, 95% CI: 0.39-0.74), but not Dys (OR = 0.47; 95% CI: 0.20-1.10). In IBD patients, mesalazine dosage ≥ 1.2 g/day showed greater protective effects against CRC/Dys than dosages < 1.2 g/day. However, Sulphasalazine therapy did not show any noticeable protective function regardless of the dosage administered.
MATERIALS AND METHODS
We performed a systematic review with a meta-analysis of 26 observational studies involving 15,460 subjects to evaluate the risks of developing CRC and Dys in IBD patients receiving 5-ASA treatment. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for each evaluation index.
CONCLUSIONS
5-ASA has a chemopreventive effect on CRC (but not Dys) in IBD patients. Moreover, UC patients can benefit more from 5-ASA than CD patients. Mesalazine maintenance dosage ≥ 1.2 g/day is an effective treatment for reducing CRC risk in IBD patients.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Chemoprevention; Cohort Studies; Colorectal Neoplasms; Humans; Hyperplasia; Inflammatory Bowel Diseases; Mesalamine; Odds Ratio; Population Surveillance; Publication Bias; Risk Assessment; Risk Factors
PubMed: 27906680
DOI: 10.18632/oncotarget.13715 -
Intestinal Research Oct 2020Despite several recent advances in therapy in inflammatory bowel disease (IBD), 5-aminosalicylic acid (5-ASA) therapy has retained its place especially in ulcerative... (Review)
Review
Despite several recent advances in therapy in inflammatory bowel disease (IBD), 5-aminosalicylic acid (5-ASA) therapy has retained its place especially in ulcerative colitis. This consensus on 5-ASA is obtained through a modified Delphi process, and includes guiding statements and recommendations based on literature evidence (randomized trials, and observational studies), clinical practice, and expert opinion on use of 5-ASA in IBD by Indian gastroenterologists. The aim is to aid practitioners in selecting appropriate treatment strategies and facilitate optimal use of 5-ASA in patients with IBD.
PubMed: 32646198
DOI: 10.5217/ir.2019.09176 -
Journal of Global Antimicrobial... Mar 2020Pasiniazid is a chemical complex of isoniazid (INH) and para-aminosalicylic acid (PAS). The aim of this study was to explore the cross-resistance of INH, PAS and...
OBJECTIVES
Pasiniazid is a chemical complex of isoniazid (INH) and para-aminosalicylic acid (PAS). The aim of this study was to explore the cross-resistance of INH, PAS and pasiniazid against INH-resistant Mycobacterium tuberculosis isolates in China.
METHODS
A Microplate alamarBlue® Assay was performed to determine the minimum inhibitory concentrations (MICs) of INH, PAS and pasiniazid against 109 INH-resistant M. tuberculosis isolates. A statistical analysis of the relationship between different genotypes, gene mutations, and INH, PAS or pasiniazid susceptibility was then performed.
RESULTS
Among the 109 INH-resistant isolates, 13 (11.9%) and 21 (19.3%) showed resistance to PAS and pasiniazid, respectively. Among the 13 PAS-resistant M. tuberculosis isolates, 11 remained susceptible to pasiniazid. Of 63 INH-resistant isolates harbouring mutations in katG, the inhA promoter or the oxyR-ahpC intergenic region, 52 remained susceptible to pasiniazid. Moreover, 11 of 13 pasiniazid-resistant isolates carried mutations in katG, the inhA promoter or the oxyR-ahpC intergenic region.
CONCLUSION
Taken together, these results demonstrate that PAS resistance and mutations in thekatG gene, inhA promoter or oxyR-ahpC intergenic region in INH-resistant M. tuberculosis have little effect on pasiniazid susceptibility.
Topics: Adult; Aminosalicylic Acid; Aminosalicylic Acids; Antitubercular Agents; Bacterial Proteins; Catalase; China; DNA, Intergenic; Drug Resistance, Multiple, Bacterial; Genotype; Humans; Isoniazid; Microbial Sensitivity Tests; Mutation; Mycobacterium tuberculosis; Oxidoreductases; Peroxiredoxins; Promoter Regions, Genetic; Repressor Proteins; Tuberculosis, Pulmonary
PubMed: 31425771
DOI: 10.1016/j.jgar.2019.08.005 -
Journal of the American Heart... Dec 2022Background The gut and gut microbiota, which were previously neglected in blood pressure regulation, are becoming increasingly recognized as factors contributing to...
Background The gut and gut microbiota, which were previously neglected in blood pressure regulation, are becoming increasingly recognized as factors contributing to hypertension. Diseases affecting the gut such as inflammatory bowel disease (IBD) present with aberrant energy metabolism of colonic epithelium and gut dysbiosis, both of which are also mechanisms contributing to hypertension. We reasoned that current measures to remedy deficits in colonic energy metabolism and dysbiosis in IBD could also ameliorate hypertension. Among them, 5-aminosalicylic acid (5-ASA; mesalamine) is a PPARγ (peroxisome proliferator-activated receptor gamma) agonist. It attenuates IBD by a dual mechanism of selectively enhancing colonic epithelial cell energy metabolism and ameliorating gut dysbiosis. Methods and Results A total of 2 groups of 11- to 12-week-old male, hypertensive, Dahl salt-sensitive (S) rats were gavaged with (n=10) or without (n=10) 5-aminosalicylic acid (150 mg/kg) for 4 weeks. Rats receiving 5-aminosalicylic acid treatment had a lower mean blood pressure than controls (145±3 mm Hg versus 153±4 mm Hg; <0.0001). This reduction in blood pressure was accompanied by increased activity of PPARγ, increased expression of energy metabolism-related genes, and lowering of the Firmicutes/Bacteroidetes ratio in the colon, the reduction of which is a marker for the correction of gut dysbiosis. Furthermore, these data were consistent with the American Gut Project wherein the Firmicutes/Bacteroidetes ratio of non-IBD (n=611) patients was significantly lower than patients with IBD (n=631). Conclusions 5-Aminosalicylic acid could be repurposed for hypertension by specifically enhancing the gut energy metabolism and correction of microbiota dysbiosis.
Topics: Rats; Male; Animals; Mesalamine; PPAR gamma; Dysbiosis; Drug Repositioning; Rats, Inbred Dahl; Inflammatory Bowel Diseases; Hypertension; Drug Delivery Systems
PubMed: 36533597
DOI: 10.1161/JAHA.122.027893 -
Mediators of Inflammation 2019Nuclear receptors (NRs) are ligand-dependent transcription factors that regulate the transcription of target genes. Previous epidemiological and genetic studies have... (Review)
Review
Nuclear receptors (NRs) are ligand-dependent transcription factors that regulate the transcription of target genes. Previous epidemiological and genetic studies have documented the association of NRs with the risk of inflammatory bowel disease (IBD). Although the mechanisms of action of NRs in IBD have not been fully established, accumulating evidence has demonstrated that NRs play complicated roles in regulating intestinal immunity, mucosal barriers, and intestinal flora. As one of the first-line medications for the treatment of IBD, 5-aminosalicylic acid (5-ASA) activates peroxisome proliferator-activated receptor gamma (PPAR) to attenuate colitis. The protective roles of rifaximin and rifampicin partly depend on promoting pregnane X receptor (PXR) expression. The aims of this review are to discuss the roles of several important NRs, such as PPAR, PXR, vitamin D receptor (VDR), farnesoid X receptor (FXR), and RAR-related orphan receptor gammat (RORt), in the pathogenesis of IBD and management strategies based on targeting these receptors.
Topics: Aminosalicylic Acid; Animals; Colitis; Humans; Inflammatory Bowel Diseases; PPAR gamma; Pregnane X Receptor; Receptors, Calcitriol
PubMed: 30804707
DOI: 10.1155/2019/2624941 -
Heliyon May 2024Given the widespread use of Chinese patent medicines (CPMs) in combination with 5-aminosalicylic acid (5-ASA) for Ulcerative colitis (UC) patients, this study aimed to...
Efficacy and safety of Chinese patent medicine combined with 5-aminosalicylic acid for patients with ulcerative colitis: A network meta-analysis of randomized controlled trials.
OBJECTIVES
Given the widespread use of Chinese patent medicines (CPMs) in combination with 5-aminosalicylic acid (5-ASA) for Ulcerative colitis (UC) patients, this study aimed to evaluate the efficacy and safety of nine CPMs combined with 5-ASA in the treatment of UC.
METHODS
A systematic literature search was conducted in eight databases from inception to May 2023 to identify eligible RCTs evaluating the effects of CPM combined with 5-ASA for the treatment of UC. The methodological quality of the included RCTs was assessed using the Cochrane risk of bias tool in Review Manager 5.4. The primary outcome of the meta-analysis was the overall response rate. The secondary outcomes included excellent rate, disease activity index (DAI), IL-6, IL-8, and TNF-α levels, mean platelet volume (MPV), fibrinogen (FIB) levels, recurrence rate, and adverse event rate. Network meta-analysis was performed using Review Manager 5.4 and Stata 15.0.
RESULTS
In total, 70 RCTs including 5973 patients and 10 treatment regimens were included. The combination of Kangfuxin Liquid (KFL) and 5-ASA showed the greatest efficacy in improving FIB levels and the overall response rate. Bupi Yichang Pill (BYP) combined with 5-ASA was associated with the fewest adverse events and the lowest recurrence rate. Hudi Enteric-coated Capsule (HEC) combined with 5-ASA ranked first in improving DAI. ZhiKang Capsule (ZKC), ChangYanNing Capsule (CYN), and Danshen Injection (DSI) combined with 5-ASA ranked first in improving IL-6, IL-10, and TNF-α levels, respectively. Shenling Baizhu Powder (SBP) combined with 5-ASA was associated with the highest excellent rate.
CONCLUSIONS
CPM combined with 5-ASA may be more effective than 5-ASA alone for treating UC. Besides, CPM combined with 5-ASA could better reduce the recurrence rate and adverse event rate in UC patients. The current meta-analysis provides statistical evidence for clinical application.Systematic Review Registration: International Prospective Register of Systematic Reviews (PROSPERO), No. CRD42023433672.
PubMed: 38813206
DOI: 10.1016/j.heliyon.2024.e31182 -
Journal of Physiology and Pharmacology... Aug 20215-aminosalicylic acid (5-ASA) is commonly used as the first-line treatment for ulcerative colitis (UC). In this study, we show that the mechanism responsible for the...
5-aminosalicylic acid (5-ASA) is commonly used as the first-line treatment for ulcerative colitis (UC). In this study, we show that the mechanism responsible for the protective effect of 5-ASA is associated with the modulation of non-coding microRNA molecule (miRNA) expression. Stimulation of human intestinal epithelial cells (Caco-2) with 1000 μM of 5-ASA suppressed the levels of miR-125b, miR-150, miR-155, miR-346 and miR-506, which are known to be involved in the regulation of colitis and/or colorectal cancer in patients with inflammatory bowel disease. The 5-ASA-induced inhibitions of these miRNAs were associated with significant inductions of their target genes such as vitamin D receptor (VDR), suppressor of cytokine signaling (SOCS1), Forkhead box O (FOXO3a) and DNA methyltransferase 1 (DNMT1). The relationships between the selected miRNAs and their target genes were further confirmed in Caco-2 cells transfected of with specific miRNA inhibitors or miRNA mimics. Moreover, we showed that 5-ASA has the potential to hinder miR-155 expression induced by the transfection of miR-155 mimic into Caco-2 cells. These findings underline the anti-inflammatory and chemoprotective effects of 5-ASA treatment.
Topics: Caco-2 Cells; Colitis, Ulcerative; Gene Expression Regulation; Humans; Mesalamine; MicroRNAs
PubMed: 34987126
DOI: 10.26402/jpp.2021.4.04 -
Molecules (Basel, Switzerland) Nov 2021Compound 5-{[(2E)-3-bromo-3-carboxyprop-2-enoyl]amino}-2-hydroxybenzoic acid (), a new 5-aminosalicylic acid (5-ASA) derivative, has proven to be an antioxidant in vitro...
Preclinical Pharmacokinetics and Acute Toxicity in Rats of 5-{[(2E)-3-Bromo-3-carboxyprop-2-enoyl]amino}-2-hydroxybenzoic Acid: A Novel 5-Aminosalicylic Acid Derivative with Potent Anti-Inflammatory Activity.
Compound 5-{[(2E)-3-bromo-3-carboxyprop-2-enoyl]amino}-2-hydroxybenzoic acid (), a new 5-aminosalicylic acid (5-ASA) derivative, has proven to be an antioxidant in vitro and an anti-inflammatory agent in mice. The in vivo inhibition of myeloperoxidase was comparable to that of indomethacin. The aim of this study was to take another step in the preclinical evaluation of by examining acute toxicity with the up-and-down OECD method and pharmacokinetic profiles by administration of the compound to Wistar rats through intravenous (i.v.), oral (p.o.), and intraperitoneal (i.p.) routes. According to the Globally Harmonized System, belongs to categories 4 and 5 for the i.p. and p.o. routes, respectively. An RP-HPLC method for quantification in plasma was successfully validated. Regarding the pharmacokinetic profile, the elimination half-life was approximately 0.9 h with a clearance of 24 mL/min after i.v. administration of (50 mg/kg). After p.o. administration (50 mg/kg), the maximum plasma concentration was reached at 33 min, the oral bioavailability was about 77%, and the compound was amply distributed to all tissues evaluated. Therefore, administered p.o. in rats is suitable for reaching the colon where it can exert its effect, suggesting an important advantage over 5-ASA and indomethacin in treating ulcerative colitis and Crohn's disease.
Topics: Aminosalicylic Acids; Animals; Anti-Inflammatory Agents, Non-Steroidal; Biological Availability; Colitis, Ulcerative; Crohn Disease; Drug Evaluation, Preclinical; Female; Hydroxybenzoates; Lethal Dose 50; Male; Rats; Rats, Wistar; Tissue Distribution
PubMed: 34833894
DOI: 10.3390/molecules26226801 -
Alimentary Pharmacology & Therapeutics Sep 2006The effectiveness of sulfasalazine depends on the splitting of the diazo bond in the molecule by the action of bacteria in the large bowel, releasing the... (Review)
Review
The effectiveness of sulfasalazine depends on the splitting of the diazo bond in the molecule by the action of bacteria in the large bowel, releasing the pharmacologically active moiety, 5-aminosalicylic acid. The development of pH-dependent, delayed-release formulations of 5-aminosalicylic acid abolished the toxicity associated with the sulfapyridine part of sulfasalazine. 5-aminosalicylic acid is now believed to act by activating a class of nuclear receptors involved in the control of inflammation, cell proliferation, apoptosis and metabolic function, the gamma form of peroxisome proliferator-activated receptors. These receptors are expressed at particularly high levels in colon epithelial cells, where their expression appears to be at least in part stimulated by gut bacteria. Other drugs known to act via peroxisome proliferator-activated receptor-gamma, such as rosiglitazone and the selective peroxisome proliferator-activated receptor-gamma ligand GW1929, can be displaced from their binding sites on the peroxisome proliferator-activated receptor-gamma molecule by 5-aminosalicylic acid at concentrations of 5-aminosalicylic acid that correspond with the concentrations found in the lumen of ulcerative colitis patients taking oral mesalazine. Genetically engineered heterozygous knockout mice (peroxisome proliferator-activated receptor-gamma+/-) are particularly susceptible to colonic inflammation, and inflammation is more severe in these mice, in response to chemicals that induce experimental colonic ulcers. In these experimental models, 5-aminosalicylic acid is ineffective in peroxisome proliferator-activated receptor-gamma+/- mice. This new insight provides a mechanistic foundation for the possibility that long-term treatment with 5-aminosalicylic acid can reduce the risk of colorectal cancer in patients with ulcerative colitis.
Topics: Acetylation; Animals; Anti-Inflammatory Agents, Non-Steroidal; Colitis, Ulcerative; Colon; Delayed-Action Preparations; Humans; Mesalamine; Mice; Patient Compliance; Peroxisome Proliferator-Activated Receptors; Sulfasalazine
PubMed: 16939423
DOI: 10.1111/j.1365-2036.2006.03069.x -
The British Journal of Ophthalmology Sep 1963
Topics: Aminosalicylic Acid; Aminosalicylic Acids; Diabetic Retinopathy; Diet; Diet Therapy; Drug Therapy; Geriatrics; Glaucoma; Humans; Hypoglycemic Agents
PubMed: 14189722
DOI: 10.1136/bjo.47.9.513